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Correlation between immune reconstitution and chronic graft-versus-host disease after unrelated cord blood transplantation and sibling peripheral blood stem cell transplantation

Zhonghua Xue Ye Xue Za Zhi. 2021 Jun 14;42(6):466-473. doi: 10.3760/cma.j.issn.0253-2727.2021.06.005.

ABSTRACT

Objective: To explore the relationship between the reconstitution of immune cells in patients with hematological malignancies and the occurrence of chronic graft-versus-host disease (cGVHD) after treatment with unrelated cord blood transplantation (UCBT) and sibling peripheral blood stem cell transplantation (PBSCT) . Methods: A total of 124 patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) in the First Affiliated Hospital of University of Science and Technology of China from March 2018 to August 2019, including 96 patients with UCBT and 28 patients with PBSCT. Peripheral blood immune cells of patients with UCBT and PBSCT were detected at 1, 3, 6, 9, and 12 months after transplantation using flow cytometry, and both UCBT and PBSCT patients were divided into cGVHD and non-cGVHD groups based on whether cGVHD occurred to explore the correlation between the immune cells reconstitution of the two types of transplantation and cGVHD. Results: ①The cumulative incidence of the moderate to severe cGVHD in the UCBT group was significantly lower than that in the PBSCT group[9.38% (95% CI 3.35%-15.02%) vs 28.57% (95% CI 9.72%-43.50%) , P=0.008]; the 2-year cumulative incidence of cGVHD and moderate to severe cGVHD in the UCBT group was lower than that in the PBSCT group[15.60% (95% CI 9.20%-23.60%) vs 32.10% (95% CI 15.80%-49.70%) , P=0.047; 10.40% (95% CI 5.30%-17.50%) vs 28.60% (95% CI 13.30%-46.00%) , P=0.014]. ②The absolute counts of CD4(+)T cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[59.00 (36.70-89.65) ×10(7)/L vs 31.40 (18.10-44.00) ×10(7)/L, P<0.001; 71.30 (49.60-101.45) ×10(7)/L vs 41.60 (25.82-56.27) ×10(7)/L, P<0.001; 83.00 (50.17-121.55) ×10(7)/L vs 44.85 (31.62-62.10) ×10(7)/L, P<0.001]; the proportions of CD4(+)T cells in the UCBT group were always higher than those in the PBSCT group (P<0.05) . The absolute counts and proportions of B cells in the PBSCT group were higher than those in the UCBT group at the first month after transplantation[0.70 (0.30-1.70) ×10(7)/L vs 0.10 (0-0.30) ×10(7)/L, P<0.001; 0.45% (0.30%-2.20%) vs 0.20% (0.10%-0.40%) , P=0.002]; the absolute counts and proportions of B cells in the UCBT group were higher than those in the PBSCT group at 9 and 12 months after transplantation[53.80 (28.00-103.20) ×10(7)/L vs 23.35 (5.07-35.00) ×10(7)/L, P<0.001; 21.45 (11.80-30.45) % vs 9.00% (3.08%-16.73%) , P<0.001. 66.70 (36.97-98.72) ×10(7)/L vs 20.85 (7.72-39.40) ×10(7)/L, P<0.001; 22.20% (14.93%-29.68%) vs 8.75% (5.80%-18.93%) , P<0.001]. The absolute counts and proportions of regulatory B (Breg) cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[1.23 (0.38-3.52) ×10(7)/L vs 0.05 (0-0.84) ×10(7)/L, P<0.001; 5.35% (1.90%-12.20%) vs 1.45% (0-7.78%) , P=0.002. 2.25 (1.07-6.71) ×10(7)/L vs 0.12 (0-0.77) ×10(7)/L, P<0.001; 6.25% (2.00%-12.33%) vs 0.80% (0-5.25%) , P<0.001. 3.69 (0.83-8.66) ×10(7)/L vs 0.46 (0-0.93) ×10(7)/L, P<0.001; 6.15% (1.63%-11.75%) vs 1.40% (0.18%-5.85%) , P<0.001].The absolute counts and proportions of CD3(+)T cells, CD8(+)T cells, and Treg cells in the UCBT group were not significantly different from those in the PBSCT group. ③The absolute counts of B cells in the non-cGVHD group of UCBT patients were higher than those in the moderate to severe cGVHD group at 6 and 12 months after transplantation (P=0.038, P=0.043) ; the proportions of B cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 6 months after transplantation (P=0.049) . The absolute counts of Breg cells in the non-cGVHD group of patients with UCBT were higher than those in the moderate to severe cGVHD group at 6, 9, and 12 months after transplantation (P=0.006, P=0.028, P=0.050) ; the proportions of Breg cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 9 months after transplantation (P=0.038) . ④The absolute counts and proportions of B and Breg cells in the non-cGVHD group of patients with PBSCT were not statistically different than those in the moderate to severe cGVHD group. Conclusion: In the process of immune cell reconstitution, the Breg cells in the UCBT group were higher than those in the PBSCT group, and the Breg cells in the non-cGVHD group of the two types of transplantation were always higher than those in the moderate to severe cGVHD group, indicating that Breg cells can reduce the occurrence of cGVHD, revealing the possible reason for the lower incidence of cGVHD in the UCBT group.

PMID:34384152 | DOI:10.3760/cma.j.issn.0253-2727.2021.06.005

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Analysis of fusion gene expression in acute myeloid leukemia

Zhonghua Xue Ye Xue Za Zhi. 2021 Jun 14;42(6):480-486. doi: 10.3760/cma.j.issn.0253-2727.2021.06.007.

ABSTRACT

Objective: To analyze the genetic landscape of multiple fusion genes in patients with de novo acute myeloid leukemia (AML) and investigate the characteristics of immunophenotypes and mutations. Methods: The results of multiple fusion genes from 4192 patients with de novo AML were retrospectively analyzed from 2016 to 2020. In addition, the immunophenotypical data and the mutational results from high-through put method were statistically investigated and correlated as well. Results: ①Among the 52 targets, 29 different types of fusion genes were detected in 1948 patients (46.47%) with AML, which demonstrated an “exponential distribution” . ② As the age increased, the number of patients with fusion gene increased first and then decreased gradually. The total incidence rate of fusion genes and MLL rearrangment in children were significantly higher than those in adults (69.18% vs 44.76%, 15.35% vs 8.36%) . ③The mutations involving FLT3 and RAS signaling pathway contributed most in patients with MLL rearrangment. ④No specific immunophenotypic characteristics were found in AML patients with MLL or NUP98 rearrangements. Conclusion: Nearly half of AML patients were accompanied by specific fusion gene expression, the proportions of different fusion genes in pediatric and adults patients were different by multiple PCR. The gene mutations and immunophenotype of these AML patients have certain rules.

PMID:34384154 | DOI:10.3760/cma.j.issn.0253-2727.2021.06.007

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Synthesis and Characterization of Antifungal Nanocomposite AgSiO2 Polymethyl Methacrylate

Eur J Dent. 2021 Aug 12. doi: 10.1055/s-0041-1731831. Online ahead of print.

ABSTRACT

OBJECTIVES: Polymethyl methacrylate as the most common material used in denture bases has some problems. The aim of this study was to introduce a new nanocomposite of PMMA to improve flexural strength and antifungal properties.

MATERIALS AND METHODS: In this experimental study, AgSiO2 nanoparticles were prepared, and their characteristics were confirmed by scanning electron microscope and energy dispersive spectroscopy techniques. Then the nanoparticles in the weight ratio of 0.1, 0.3, 0.5, and 0.7% were incorporated to heat-cured PMMA and the control group included no nanoparticles.To measure the flexural strength before and after thermocycling three-point bending test was used. Eight samples per group with dimensions of 65 × 10 × 2.5 mm were used. Antifungal activity against Candida albicans (PTCC 5027) was investigated through colony count method. Statistical analysis was done by SPSS at significance level of p-value ≤0.05.

RESULTS: The mean flexural strength in groups 0.1, 0.3, and 0.7% was significantly higher than the control. After thermocycling flexural strength of the control group was significantly lower than 0.3 and 0.5% groups. As the concentration of nanoparticles increased the antifungal activity improved (p < 0.05).

CONCLUSION: Addition of nanoparticles AgSiO2 improved flexural strength and antifungal characteristics of PMMA.

PMID:34384125 | DOI:10.1055/s-0041-1731831

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Comparability of 11 different equations for estimating LDL cholesterol on different analysers

Clin Chem Lab Med. 2021 Aug 11. doi: 10.1515/cclm-2021-0747. Online ahead of print.

ABSTRACT

OBJECTIVES: Low-density lipoprotein cholesterol (LDL-C) estimation is critical for risk classification, prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). Predictive equations and direct LDL-C are used. We investigated the comparability between the Martin/Hopkins, Sampson, Friedewald and eight other predictive equations on two analysers, to determine whether the equation or analyser influences predicted LDL-C result.

METHODS: In two unpaired datasets, 9,995 lipid profiles were analysed by the Abbott Architect and 4,782 by the Roche Cobas analysers. Non-parametric statistics and Bland Altman plots were used to compare LDL-C.

RESULTS: On the Abbott analyser; the Martin/Hopkins, Sampson and Friedewald LDL-C were comparable (median bias ≤1.8%) over a range of 1-4.9 mmol/L. On the Roche platform, Martin/Hopkins LDL-C was comparable to Friedewald (median bias 0.3%) but not to Sampson LDL-C (median bias 25%). In patients with LDL-C <1.8 mmol/L and triglycerides (TG) ≤1.7 mmol/L, predicted LDL-C using Abbott reagents was similar between Martin/Hopkins, Sampson and Friedewald equations but not comparable using Roche reagents. Abbott reagents classified 10-20% of patients in the 1.0-1.8 mmol/L range (Martin/Hopkins 13.4%; Sampson 14.5%; Friedewald 16%; direct LDL-C 13.2%). Roche reagents classified 11-30% in the 1.0-1.8 mmol/L range (Martin/Hopkins 23%; Sampson 11%; Friedewald 25%; direct LDL-C 17%).

CONCLUSIONS: Performance of predictive equations is influenced by the choice of analyser for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and TG. Replacement of the Friedewald equation with Martin/Hopkins estimation to improve quality of LDL-C results can be safely implemented across analysers, whereas caution is advised regarding the Sampson equation.

PMID:34384146 | DOI:10.1515/cclm-2021-0747

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Analysis of the clinical characteristics of 24 cases of hematological malignancies with SET-NUP214 fusion gene

Zhonghua Xue Ye Xue Za Zhi. 2021 Jun 14;42(6):459-465. doi: 10.3760/cma.j.issn.0253-2727.2021.06.004.

ABSTRACT

Objective: To investigate the expression of SET-NUP214 fusion gene in hematological malignancies and to analyze its related clinical biological characteristics. Methods: The clinical data of 24 patients with SET-NUP214 fusion gene-positive hematological malignancies were retrospectively analyzed, and the Kaplan-Meier method was used for survival analysis. Results: Among the 24 patients with SET-NUP214 fusion gene, 15 cases of acute lymphoblastic leukemia (ALL) (13 cases of T-ALL and 2 cases of B-ALL) , 7 cases of acute myeloid leukemia (AML) , and 2 cases of T/myeloid mixed acute leukemia have been identified. The immunophenotype of 13 cases of T-ALL was mainly characterized by CD3(+)CD2(-), 73.3% of ALL was characterized by myeloid marker expression, and 85.7% of AML was characterized by CD7 expression. Complete remission (CR) was achieved in 22 patients (91.7%) after induction chemotherapy. All 24 patients received allogeneic hematopoietic stem cell transplantation (HSCT) . With a median follow-up of 24 months, the 3-year relapse free survival (RFS) of AML and ALL was 85.7% and 33.3%, respectively (P=0.128) . Comparing 13 cases of SET-NUP214-positive and 62 cases of SET-NUP214-negative T-ALL, the CR rates of induction chemotherapy were 92.3% and 93.5% (P=0.445) , and the 4-week CR rates of induction chemotherapy were 69.2% and 72.6%, respectively (P=0.187) ; the differences were not statistically significant. After HSCT, the 3-year RFS of SET-NUP214(+)T-ALL and SET-NUP214(-)T-ALL was 38.5% and 66.4%, respectively (P=0.028) , and the difference was statistically significant. Conclusion: The SET-NUP214 fusion gene is mainly detected in T cell-derived hematological malignancies, and the prognosis of SET-NUP214 positive T-ALL is relatively poor.

PMID:34384151 | DOI:10.3760/cma.j.issn.0253-2727.2021.06.004

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Modified Arytenoid Adduction Operation for the Treatment of Unilateral Vocal Fold Paralysis

ORL J Otorhinolaryngol Relat Spec. 2021 Aug 12:1-6. doi: 10.1159/000517561. Online ahead of print.

ABSTRACT

INTRODUCTION: Unilateral vocal fold paralysis (UVFP) was a relative common glottic insufficiency disease; however, a completely satisfactory treatment of UVFP was elusive. This study was aimed to evaluate the surgical efficacy of modified arytenoid adduction with fenestration of the thyroid cartilage in the management of patients with UVFP, including voice and aspiration outcomes, and to summarize the postoperative complications.

METHODS: A retrospective analysis was performed on a total of 21 patients who underwent modified arytenoid adduction operation with fenestration of the thyroid cartilage for UVFP from July 2012 to June 2017. The scores of Grade, Roughness, Breathiness, Asthenia, Strain scale (GRBAS), voice self-satisfaction, dynamic laryngoscopy and the voice acoustic data (fundamental frequency [F0], fundamental frequency perturbation [jitter], loudness, amplitude perturbation [shimmer], and maximal phonatory time [MPT], etc.) were statistically analyzed preoperatively and 3-6 months postoperatively. The occurrence of postoperative complications was also summarized.

RESULTS: The voice subjective perception of 21 patients was significantly improved after operation. The rate of voice self-satisfaction was 90.5%. The mean values of voice acoustics parameters were significantly improved. The MPT was significantly longer (p < 0.001), and the ratings of postoperative aspiration were significantly decreased compared with the preoperation. Among the 21 patients, 15 cases had sense of laryngeal obstruction, 8 cases had of 1-2° laryngemphraxis (recovered after 10-15 days). There were 2 cases of laryngeal stridor, 1 case of incision infection, 1 case of pharyngeal fistula, and 1 case of falsetto (corrected by voice training). No patient had laryngeal hematoma, neck hematoma, or laryngospasm.

CONCLUSION: The modified arytenoid adduction operation with fenestration of the thyroid cartilage can significantly improve the vocal function of patients with UVFP and effectively reduce the aspiration, with fewer postoperative complications, less trauma, and more convenient advantages.

PMID:34384083 | DOI:10.1159/000517561

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Subaxial Spine Fractures: A Comparison of Patient-reported Outcomes and Complications Between Anterior and Posterior Surgery

Spine (Phila Pa 1976). 2021 Sep 1;46(17):E926-E931. doi: 10.1097/BRS.0000000000003979.

ABSTRACT

STUDY DESIGN: Observational study on prospectively collected data.

OBJECTIVES: The aim of this study was to compare long-term patient-reported outcomes and complications after anterior or posterior cervical spine surgery for subaxial fractures.

SUMMARY OF BACKGROUND DATA: There is no consensus in the literature regarding the optimal surgical approach when treating spine fractures in the subaxial region.

METHODS: A total of 200 individuals who had been treated with either anterior or posterior surgery due to a subaxial single segment, or single vertebra, injury between 2006 and 2016 and had at least 1 year follow-up were identified in the Swedish Spine register. Cases were matched 1:1 for age (±5 years). Outcomes were Neck Disability Index (NDI) and EQ-5D-3L, and reoperations, mortality, and surgeon- and patient-reported wound complications within 90 days. t Tests and χ2 tests were used statistical comparisons.

RESULTS: At follow-up, NDI was 23 (21) in the anterior group and 29 (21) in the posterior group (P = 0.07). EQ-5D-3L index was 0.62 (0.37) in the anterior group and 0.54 (0.39) in the posterior group (P = 0.13). Patient satisfaction was higher in the anterior group (89% vs. 73%, P = 0.03). No deaths occurred within the first 90 days after surgery, six individuals in the anterior group and three individuals in the posterior group were reoperated (P = 0.31), and five individuals in the anterior group and 24 in the posterior group suffered a wound infection (P < 0.001).

CONCLUSION: Anterior surgery and posterior surgery were associated with similar neck disability and general quality of life at follow-up, whereas anterior surgery was associated with higher patient satisfaction and lower infection rates.Level of Evidence: 3.

PMID:34384090 | DOI:10.1097/BRS.0000000000003979

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Comparing Smoking Cessation Interventions among Underserved Patients Referred for Lung Cancer Screening: A Pragmatic Trial Protocol

Ann Am Thorac Soc. 2021 Aug 12. doi: 10.1513/AnnalsATS.202104-499SD. Online ahead of print.

ABSTRACT

Smoking burdens are greatest among underserved patients. Lung cancer screening (LCS) reduces mortality among individuals at risk for smoking-associated lung cancer. Although LCS programs must offer smoking cessation support, the interventions that best promote cessation among underserved patients in this setting are unknown. This stakeholder-engaged, pragmatic randomized clinical trial (RCT) will compare the effectiveness of four interventions promoting smoking cessation among underserved patients referred for LCS. Using an additive study design, all four arms provide standard “Ask-Advise-Refer” care. Arm 2 adds free or subsidized pharmacologic cessation aids; Arm 3 adds financial incentives up to $600 for cessation; and Arm 4 adds a mobile device-delivered episodic future thinking tool to promote attention to long-term health goals. We hypothesize that smoking abstinence rates will be higher with the addition of each intervention when compared to Arm 1. We will enroll 3,200 adults with LCS orders at four United States health systems. Eligible patients include those who smoke at least one cigarette daily and self-identify as a member of an underserved group (i.e., Black or Latinx, a rural resident, completed a high school education or less, and/or with a household income <200% of the federal poverty line). The primary outcome is biochemically confirmed smoking abstinence sustained through 6 months. Secondary outcomes include abstinence sustained through 12 months, other smoking-related clinical outcomes, and patient-reported outcomes. This pragmatic RCT will identify the most effective smoking cessation strategies that LCS programs can implement to reduce smoking burdens affecting underserved populations. Clinical trial registered with ClinicalTrials.gov (NCT04798664). Date of registration: March 12, 2021. Date of trial launch: May 17, 2021.

PMID:34384042 | DOI:10.1513/AnnalsATS.202104-499SD

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Exploring the role of soil types on defense and fitness traits of silverleaf nightshade (Solanum elaeagnifolium), a worldwide invasive species through a field survey in the native range

Plant Signal Behav. 2021 Aug 12:1964163. doi: 10.1080/15592324.2021.1964163. Online ahead of print.

ABSTRACT

Silverleaf nightshade (Solanum elaeagnifolium) is a highly successful invasive weed that has caused agricultural losses both in its home and invaded ranges. Surveying 50 sub-populations over 36,000 km2 in its native range in South Texas, we investigated the interactions among soil type, population size, plant height, herbivory, and plant defenses in its home range with the expectation that populations growing in the plant’s preferred sandier soils would host larger colonies of healthier and better defended plants. At each sampling location, on randomly selected plants, we measured height, insect herbivore damage, and presence, and density of internode spines. Soil type was determined using the NRCS Web Soil Survey and primarily grouped into sand, clay, or urban. Our results show a tradeoff between growth and defense with larger colonies and taller plants in clay soils, but smaller colonies of shorter, spinier plants in sandy soils. We also observed decreased herbivory in urban soils, further confirming the plant’s ability to survive and even be strengthened by highly disturbed conditions. This study is a starting point for a better understanding of silverleaf nightshade’s ecology in its home range and complicates the assumption that it thrives best in sandy soils.

PMID:34384043 | DOI:10.1080/15592324.2021.1964163

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Intra-operative cerebral blood flow assessment by indocyanine green video-angiography after temporary arterial occlusion in aneurysm surgery and its clinical implications: a prospective study

J Cerebrovasc Endovasc Neurosurg. 2021 Aug 13. doi: 10.7461/jcen.2021.E2020.10.003. Online ahead of print.

ABSTRACT

OBJECTIVE: Indocyanine green video angiography (ICG-VA) is a routine while performing vascular surgery to assess patency of perforators, completeness of clipping and/or to assess patency of anastomosis. Its usefulness in assessing cerebral blood flow and perfusion is not well studied. This study is aimed to assess the cerebral blood flow and perfusion after temporary clipping and to correlate with the risk of ischemia.

METHODS: Prospective analysis of intra-operative ICG-VA performed during temporary arterial occlusion in 38 patients from January 2014 to December 2018 was conducted. Co-relation with post-operative MR diffusion weighted imaging (MR DWI) in terms of vascular territory of interest within 48 hours of surgery was performed. Clinical outcome was assessed using modified Rankin Scale (mRS) score 1-month post-surgery.

RESULTS: 43 aneurysms in 38 patients clipped using ICG-VA were included in this study. No side effect of ICG dye was seen in any patients. The number of times temporary clips applied had a direct relationship to the delay in appearance of ICG in the surgical field which became statistically significant after application of 3rd temporary clip. Nine (23.7%) patients developed ischemia following the procedure confirmed by post-operative MR DWI and all the ischemic cases had visible decrease in ICG fluorescence post-temporary clipping.

CONCLUSIONS: No previous study had tried to assess the intraoperative cerebral blood flow and perfusion during temporary clipping of parent vessels during aneurysm surgery. The use of ICG-VA can be extended to assess perfusion in desired territory by merely assessing the degree of opacification.

PMID:34384018 | DOI:10.7461/jcen.2021.E2020.10.003